Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China.
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China.
Cytokine Growth Factor Rev. 2021 Oct;61:2-15. doi: 10.1016/j.cytogfr.2021.06.002. Epub 2021 Jun 18.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical presentations, ranging from asymptomatic cases to severe pneumonia or even death. In severe COVID-19 cases, an increased level of proinflammatory cytokines has been observed in the bloodstream, forming the so-called "cytokine storm". Generally, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation intensely induces cytokine production as an inflammatory response to viral infection. Therefore, the NLRP3 inflammasome can be a potential target for the treatment of COVID-19. Hence, this review first introduces the canonical NLRP3 inflammasome activation pathway. Second, we review the cellular/molecular mechanisms of NLRP3 inflammasome activation by SARS-CoV-2 infection (e.g., viroporins, ion flux and the complement cascade). Furthermore, we describe the involvement of the NLRP3 inflammasome in the pathogenesis of COVID-19 (e.g., cytokine storm, respiratory manifestations, cardiovascular comorbidity and neurological symptoms). Finally, we also propose several promising inhibitors targeting the NLRP3 inflammasome, cytokine products and neutrophils to provide novel therapeutic strategies for COVID-19.
新型冠状病毒病 2019（COVID-19）由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起，表现出广泛的临床特征，从无症状病例到严重肺炎，甚至死亡。在严重的 COVID-19 病例中，在血液中观察到促炎细胞因子水平升高，形成所谓的“细胞因子风暴”。通常，核苷酸结合寡聚化结构域样受体含吡咯并嘧啶结构域 3（NLRP3）炎性小体激活强烈诱导细胞因子产生作为对病毒感染的炎症反应。因此，NLRP3 炎性小体可以成为治疗 COVID-19 的潜在靶标。因此，本综述首先介绍了经典的 NLRP3 炎性小体激活途径。其次，我们综述了 SARS-CoV-2 感染诱导 NLRP3 炎性小体激活的细胞/分子机制（例如，病毒穿孔蛋白、离子流和补体级联）。此外，我们描述了 NLRP3 炎性小体在 COVID-19 发病机制中的作用（例如，细胞因子风暴、呼吸表现、心血管合并症和神经症状）。最后，我们还提出了几种针对 NLRP3 炎性小体、细胞因子产物和中性粒细胞的有希望的抑制剂，为 COVID-19 提供新的治疗策略。
